IMPAIRED INSULIN-MEDIATED SKELETAL-MUSCLE BLOOD-FLOW IN PATIENTS WITH NIDDM
IMPAIRED INSULIN-MEDIATED SKELETAL-MUSCLE BLOOD-FLOW IN PATIENTS WITH NIDDM
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NIDDM 患者胰岛素介导的骨骼肌血流受损
DOI：
10.2337/diabetes.41.9.1076
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发表时间：
1992-09-01
期刊：
影响因子：
7.7
通讯作者：
BARON, AD
中科院分区：
文献类型：
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作者：
LAAKSO, M;EDELMAN, SV;BARON, AD
非胰岛素依赖型糖尿病（NIDDM）患者表现出骨骼肌胰岛素介导的葡萄糖摄取（IMGU）率下降。由于IMGU等于动静脉葡萄糖差（AVG-DELTA）与进入肌肉的血流量(F)的乘积（IMGU = AVG-DELTA x F），因此组织通透性（AVG-DELTA）和/或葡萄糖和胰岛素输送(F)的降低可能导致IMGU的降低。研究了6名肥胖的NIDDM受试者（103 +/- 9 kg）的骨骼肌IMGU成分，并与6名瘦（体重68 +/- 3 kg）和6名糖耐量正常的肥胖（94 +/- 3 kg）进行了比较。采用正糖钳夹和腿部平衡联合技术，构建连续注射胰岛素（血清胰岛素130 ~ 80000 pmol/L）时全身和腿部肌肉IMGU的胰岛素剂量反应曲线。在瘦肉、肥胖和NIDDM受试者中，全身IMGU、股骨AVG-DELTA和腿部IMGU在胰岛素范围内呈剂量依赖性增加，瘦肉受试者的ED50为400-500 pmol/L，肥胖受试者的ED50为1000-1200 pmol/L， NIDDM受试者的ED50为4000-7000 pmol/L（瘦肉受试者与肥胖和NIDDM受试者相比P < 0.01）。在瘦肉和肥胖受试者中，最有效的胰岛素浓度使腿部血流量比基础增加了2倍，ED50分别为266 pmol/L和957 pmol/L（瘦肉与肥胖相比P < 0.01）。相比之下，NIDDM受试者的腿F没有从基础值增加（2.7 +/- 0.1 vs 3.5 +/- 0.5 dl/min， NS）。在胰岛素生理浓度范围内，NIDDM受试者的下体IMGU、腿部F、股骨AVG-DELTA和腿部IMGU均低于肥胖和瘦弱受试者，但在最大有效胰岛素浓度下，肥胖和NIDDM受试者的股骨AVG-DELTA无差异。因此，1)NIDDM患者骨骼肌组织通透性和血流量均降低，2)肥胖NIDDM患者胰岛素介导的骨骼肌血流量增加受损是由于糖尿病本身，而不是肥胖状态。骨骼肌血流量减少是NIDDM患者胰岛素抵抗的结果还是原因仍有待阐明。
Patients with non-insulin-dependent diabetes mellitus (NIDDM) exhibit decreased rates of skeletal muscle insulin-mediated glucose uptake (IMGU). Because IMGU is equal to the product of the arteriovenous glucose difference (AVG-DELTA) across and blood flow (F) into muscle (IMGU = AVG-DELTA x F), reduced tissue permeability (AVG-DELTA) and/or glucose and insulin delivery (F) can potentially lead to decreased IMGU. The components of skeletal muscle IMGU were studied in six obese NIDDM subjects (103 +/- 9 kg) and compared with those previously determined in six lean (weight 68 +/- 3 kg), and six obese (94 +/- 3 kg) with normal glucose tolerance. The insulin dose-response curves for whole body and leg muscle IMGU were constructed using the combined euglycemic clamp and leg balance techniques during sequential insulin infusions (range of serum insulin 130-80,000 pmol/L). In lean, obese, and NIDDM subjects, whole body IMGU, femoral AVG-DELTA, and leg IMGU increased in a dose-dependent fashion over the range of insulin with an ED50 of 400-500 pmol/L in lean, 1000-1200 pmol/L in obese, and 4000-7000 pmol/L in NIDDM subjects (P < 0.01 lean vs. obese and NIDDM). In lean and obese subjects, maximally effective insulin concentrations increased leg blood flow -2-fold from basal with an ED50 of 266 pmol/L and 957 pmol/L, respectively (P < 0.01 lean vs. obese). In contrast, leg F did not increase from the basal value in NIDDM subjects (2.7 +/- 0.1 vs. 3.5 +/- 0.5 dl/min, NS). In the physiological range of insulin concentrations NIDDM subjects had lower body IMGU, leg F, femoral AVG-DELTA, and leg IMGU than obese and lean subjects, but at maximally effective insulin concentrations, femoral AVG-DELTA did not differ between obese and NIDDM subjects. Thus, 1) both reduced skeletal muscle tissue permeability and blood flow are found in NIDDM subjects and 2) impaired insulin-mediated augmentation of skeletal muscle blood flow in obese NIDDM patients is due to the diabetic state per se and not to the obesity status. Whether reduced skeletal muscle blood flow is the result or the cause of insulin resistance in patients with NIDDM remains to be elucidated.